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deficiency
6- Discussing the biochemical & clinical rationale for lines of diagnosis of G6PD
2
deficiency anemia. Dr Gihan Gawish
Reduced glutathione
•
Oxidized glutathione
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Uses of NADPH in normal cellular metabolism
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Role of NADPH in antioxidant mechanisms
Introduction
Hydrogen peroxide (H2O2) is one member of the family of reactive oxygen species (ROS).
Reactive oxygen species (ROS) are formed from partial reduction of molecular O2 i.e.
adding electrons to oxygen leading to the formation of superoxide, hydrogen peroxide
and hydroxyl radical.
ROS are formed continuously from aerobic metabolism of drugs and environmental toxins
or diminished antioxidants. All these lead to oxidative stress.
ROS cause damage to DNA, protein and unsaturated lipids of the cells including cell
membranes..
They are implicated in cancer, chronic inflammatory disease and aging.
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Role of NADPH in antioxidant mechanisms (cont.)
Introduction (cont.):
The cell has different protective mechanisms that serve to minimize the toxic potential of
ROS (antioxidant effect) as follows:
B) Antioxidant chemicals:
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Role of NADPH in antioxidant mechanisms (cont.)
Introduction (cont.):
Reduced Glutathione:
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Reactive Oxygen Species (ROS)
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Pentose Phosphate Pathway (PPP)
or Hexose Monophosphate Pathway (HMP)
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Pentose Phosphate
Pathway (PPP)
Glucose-6-phosphate dehydrogenase
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Glucose 6-phosphate dehydrogenase deficiency
(G6PD deficiency)
Definition
• It is an inherited disease characterized by hemolytic anemia caused by
inability to detoxify oxidized agents.
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Mode of inheritance of G6PD Deficiency
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Normal
Heterozygous (carrier)
Mother
( Xx )
•
x X 50% of
Daughters
Normal are normal
Father carriers
(XY) X Xx XX
50% of
Sons are
affected
Y Yx YX
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Decreased amounts of reduced glutathione
due to decreased production of NADPH
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Decreased amounts of reduced glutathione
due to decreased production of NADPH
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Precipitating factors in G6PD deficiency:
• Individuals who have inherited one of the many G6PD mutations do not show
clinical manifestation.
• Some of patients with G6PD develop hemolytic anemia if they are exposed or
ingest any of the followings oxidizing agents:
1-Oxidant drugs:
2- Favism:
• Most G6PD variants are caused by point mutations in the G6PD gene.
• Other point mutations may lead to production of mutant enzymes with one
or more of the following:
Class I mutations:
It is often associated with chronic non spherocytic anaemia
(occurs even in absence of oxidative stress).
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G6PD Variants
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Diagnosis of
G6PD Deficiency Hemolytic Anemia
• Diagnosis of hemolytic anemia
• CBC and reticulocytic count
• Screening:
• Qualitative assessment of G6PD enzymatic activity
• (UV-based test)
• Confirmatory test:
• Quantitative measurement of G6PD enzymatic activity
• Molecular test:
• Detection of G6PD gene mutation
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Reference
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